Combination olaparib plus bevacizumab demonstrated clinically meaningful improvement in overall survival for patients with newly diagnosed advanced ovarian cancer and homologous recombination deficiency, with or without a tumor BRCA mutation (tBRCAm), according to final analysis results from the phase 3 PAOLA-1/ENGOT-ov25 trial.

This data was presented on Friday, September 9, 2022, at the European Society for Medical Oncology Congress in Paris, France, by first author, Isabelle Ray-Coquard, MD, Department of Medical Oncology, Centre Léon Bérard, Lyon, France.

Dr Ray-Coquard and colleagues stated that the primary analysis of PAOLA-1/ENGOT-ov25 demonstrated that "adding [olaparib] to maintenance [bevacizumab] after first-line platinum-based chemotherapy plus [bevacizumab] led to a significant progression-free survival benefit in [advanced ovarian cancer].” The data presented here represents the prespecified final OS analysis.

This phase 3 trial enrolled 809 patients with high-grade advanced ovarian cancer in response after platinum-based chemotherapy plus bevacizumab were randomized on a 2:1 basis to receive either 300mg olaparib tablets twice daily for up to 24 months plus 15mg/kg bevacizumab (n = 537), three times a week for 15 months total, or placebo plus bevacizumab (n = 269). A key secondary end point was overall survival (OS), planned to be analyzed 3 years after the primary analysis.

The median follow-up duration of 61.7 months for the treatment arm and 61.9 months for the placebo arm. OS in the treatment arm was 56.5 months compared to 51.6 months in the placebo (hazard ratio [HR]: 0.92, 95% confidence interval [CI], 0.76 to 1.12; P = .4118. 5-year OS: 47.3% vs 41.5%). For patients who had homologous recombination deficiency, OS in the treatment group was 65.5% at 5 years compared to 48.4% in the placebo group (HR: 0.62; 95% CI, 0.45 to 0.85). This benefit was seen in patients both with and without tBRCAm, but was not seen in patients who did not have homologous recombination deficiency (HR: 1.19; 95% CI, 0.88 to 1.63).

Of all the patients, 19.6% in the treatment arm were treated with subsequent PARP inhibitor, compared to 45.7% in the placebo group. In the treatment arm, there were 9 patients who experienced myelodysplastic syndrome, acute myeloid leukemia, and aplastic anemia, compared to 6 patients in the placebo group. The incidence of new primary malignancy was 4.1% in the treatment arm and 2.9% in the placebo arm.

Dr Ray-Coquard and colleagues concluded that this data confirms olaparib plus bevacizumab as the standard of care in this setting and patient population.

Source:

Ray Coquard IL, Leary A, Pignata S, et al. Final overall survival (OS) results from the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC). Presented at European Society for Medical Oncology Congress; September 9-13, 2022. Paris, France.